Diisopropylamine → HCID 21762629, compound

Temperature

0 °C

A 10 L three-necked, round-bottomed flask was charged with diisopropylamine (531 g, 5.25 mol) in THF (3 L) and cooled to −78° C. n-BuLi (2.5M, 2 L, Shangyu hualun-chem, China) was added slowly into the reaction mixture at −78° C. under nitrogen. After the addition was completed, the reaction mixture was warm up to 0° C. slowly and keep at this temperature for 20 min, then cooled to −78° C. and tert-butyl acetate (580 g, 5 mol, Sigma-Aldrich) in THF (1.0 L) was added slowly at −78° C. and stirred at this temperature for 2 h. In a separated 5 L round-bottomed flask, 2-((tert-butoxycarbonyl)amino) acetic acid (280 g, 1.6 mol, Shanghai Chiralchemicals Inc, China) was dissolved in THF (1500 mL), cooled to −30° C., and treated with 1,1′-carbonyldiimidazole (285 g, 1.76 mol). The mixture was stirred for 30 min at −30° C., then this solution was added dropwise to the cooled (−78° C.) above solution previously prepared. After 1 h, the reaction mixture was quenched with aq. 4 N NH4Cl (5 L). Similarly another 5 batches were carried out on 280 g scale. The batches were combined and the solvent was removed in vacuo. The residue was diluted with EtOAc (35 L) and successively washed with water (9 L), brine (9 L) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give the crude material as a yellow oil (2.38 kg, 90% yield) which was used without further purification.

1. additionwas added slowly into the reaction mixture at −78° C. under nitrogen
2. additionAfter the addition
3. temperaturecooled to −78° C.
4. temperaturecooled to −30° C.
5. stirringThe mixture was stirred for 30 min at −30° C.
6. additionthis solution was added dropwise to the
7. temperaturecooled (−78° C.) above solution
8. custompreviously prepared
9. waitAfter 1 h
10. customthe reaction mixture was quenched with aq. 4 N NH4Cl (5 L)
11. customthe solvent was removed in vacuo
12. additionThe residue was diluted with EtOAc (35 L)
13. washsuccessively washed with water (9 L), brine (9 L)
14. dry with materialdried over Na2SO4
15. filtrationThe solution was filtered
16. concentrationconcentrated in vacuo

ORD record

ord-68602fe9e16b4f14af037917c22e5913

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394297B2